Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda

Abstract

Background The efficacy of voluntary male medical circumcision (VMMC) for HIV prevention in men was demonstrated in three randomized trials. This led to the adoption of VMMC as an integral component of the President’s Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real world, programmatic settings is limited. Methods A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda were followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised versus uncircumcised men. Results 3,916 non-Muslim men were followed for 17,088 person-years (py). There were 1338 newly reported VMMCs (9.8/100 py). Over the study period, the median age of men adopting VMMC declined from 28 years (IQR 21-35) to 22 years (IQR 18-29; p-trend <0.001). HIV incidence was 0.40/100 py (20/4992.8 py) among newly circumcised men and 0.98/100 py (118/12095.1 py) among uncircumcised men with an adjusted IRR of 0.47 (95%CI: 0.28-0.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. Conclusions VMMC programs are highly effective in preventing HIV-acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

Non-therapeutic male circumcision in infancy or childhood and risk of human immunodeficiency virus and other sexually transmitted infections: national cohort study in Denmark

“…Moreover, as also noted by the authors [9], observed major demographic and behavioral differences between genitally intact and circumcised men in the study left ample room for residual confounding.…”

“…As acknowledged by the authors, the new Uganda study failed to adjust for the impact of pre-exposure antiretroviral prophylaxis (PrEP), which is arguably the single most important biomedical determinant of HIV acquisition [ 11 – 13 ], and this omission may well have skewed the reported association of VMMC with HIV risk. Moreover, as also noted by the authors [ 9 ], observed major demographic and behavioral differences between genitally intact and circumcised men in the study left ample room for residual confounding.…”

“…These trials also suggested a lowered risk of various STIs following VMMC [6][7][8]. A prospective study from the research group behind one of the RCTs [4] recently confirmed their original findings in a study covering 30 agrarian and semiurban trading communities in Uganda [9]. While this new finding has been interpreted as proof of VMMC's real-world effectiveness against HIV acquisition [10], the actual implications are inconclusive.…”

“…To address the paucity of relevant evidence in this area, we here present the results of the first-ever nationwide cohort study of whether non-therapeutic male circumcision in infancy or childhood provides long-term protection against the acquisition of HIV and other STIs in adolescence and adulthood. As in the recent study from Uganda [ 9 ], we restricted the focus to individuals with a non-Muslim family background to reduce the potential confounding influence of cultural or behavioral risk factors that may differ between Muslims and non-Muslims. Consequently, we provide estimates of the relative risk of acquiring HIV and other STIs up to more than three decades after infant or childhood circumcision, comparing hazard rates for such infections among circumcised and genitally intact non-Muslim males in Denmark.…”

Association of medical male circumcision and sexually transmitted infections in a population-based study using targeted maximum likelihood estimation

“…Evidence from three randomized controlled trials (RCTs) showed that MMC decreased heterosexual acquisition of HIV by 53 to 60%, herpes simplex virus type-2 (HSV-2) by 28 to 34% and genital ulcer disease among men [1][2][3][4]. Other studies [5][6][7][8], also found a protective effect of MMC against HIV infection and some sexually STIs acquired via heterosexual transmission.…”